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Vordermark BMC Cancer 2011, 11:503
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COMMENTARY
Open Access
Ten years of progress in radiation oncology
Dirk Vordermark
Abstract
Over the last decade, BMC Cancer has continuously published important research from the field of radiation
oncology. Major developments in this field include the introduction of new imaging modalities into radiotherapy
planning, the availability of hardware and software for more precise delivery of radiation dose, the individualization
of radiotherapy concepts, for example, based on microarray data, and the combination of radiotherapy with
molecular targeting approaches to overcome the radioresistance of tumor cells.
Review
On the occasion of the 10th anniversary of BMC Cancer,
this mini-review will address major developments in the
field of radiation oncology over the last decade. Important contributions published in this journal will be
discussed.
Radiation oncology is a cornerstone of modern multidisciplinary cancer treatment. It has a place in the management of most common types of cancer, either as a
single modality and organ-preserving alternative to surgery, for example, in organ-confined prostate cancer, or
as an element in a sequence of treatment steps, such as
in adjuvant radiotherapy after breast-conserving surgery
for breast cancer.
From the launch of BMC Cancer, clinical and experimental contributions from radiation oncology and radiation biology have had a special place in this journal. The
very first truly radiotherapy-related paper published in this
journal on 19 June 2001, a meta-analysis by Meert et al.
on the role of prophylactic cranial irradiation in small-cell
lung cancer, was present on the most-viewed list of the
journal for many years [1].
Strategies to improve the outcome of radiotherapy have
aimed to improve tumor control rates, thereby increasing
the chances of a cure in radical or adjuvant therapy or to
increase the rates of symptom response in palliative
situations. At the same time, reduction of toxicity and
late effects was also intended, for example, by lowering of
radiation dose to normal tissues adjacent to the tumor
target volumes.
Correspondence: [email protected]
Department of Radiation Oncology, Martin Luther University HalleWittenberg, Halle (Saale), Germany
The availability and implementation of new technology
as well as rigorous experimental, translational and clinical
studies have advanced the field of radiation oncology in
the last decade. Most progress was made in the following
areas: imaging of tumor morphology and function for
radiotherapy planning, precision of radiotherapy delivery,
individualization of radiotherapy concepts and the modification of tumor cell radiosensitivity by molecular
targeting.
Imaging for radiotherapy planning
Computed tomography (CT) scans acquired in the radiotherapy treatment position before the start of radiotherapy remain the basic imaging modality for contouring
tumor target volumes and healthy tissues (“organs at
risk”) as well as for dose calculation in radiotherapy planning. As dose-response relationships have been demonstrated for several tumor types (“higher dose to the
tumor = better chance of cure”), for example, in radical
radiotherapy of prostate cancer or non-small-cell lung
cancer, efforts to increase the radiotherapy dose in limited tumor volumes with small margins were undertaken.
However, the inability of CT to provide functional information, for example, on tumor vitality, proliferation,
oxygenation or perfusion and the problem of day-to-day
organ motion have necessitated additional information to
advance radiotherapy planning.
Functional imaging modalities, such as magnetic resonance imaging spectroscopy (MRS), and, in particular,
positron-emission tomography (PET) have opened new
possibilities to obtain metabolic information and identify
the most radioresistant subvolumes within a tumor [2].
MRS-defined dominant tumor lesions, for example, in
© 2011 Vordermark; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
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the prostate, can be specifically addressed by an escalated radiotherapy dose [3].
Precision of radiotherapy delivery
Extremely precise delivery of high radiation doses to
small volumes was already technically possible in the
1990s and favorable results were obtained in benign and
malignant brain tumors with a few fractions ("hypofractionated”) or single-fraction stereotactic radiotherapy
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(“radiosurgery”) [4]. The main indications for this technique are brain metastases, recurrent (previously irradiated) malignant gliomas, vestibular schwannomas and
meningiomas. The brain is ideal for this procedure, as
tumor or organ motion is practically non-existent.
The problem of motion of tumor-bearing organs as
well as adjacent healthy organs, most prominently exemplified by day-to-day motion of the prostate due to varying filling states of the rectum and of lung tumor
Figure 1 Visualization of three gold markers implanted into the prostate on a reconstructed CT image. The prostate itself is not visible,
but the three intraprostatic markers can be used for daily image-guided radiotherapy (IGRT) with online adaptation of the beams to the current
prostate position.
Vordermark BMC Cancer 2011, 11:503
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movement within the breathing cycle, has been
addressed by the implementation of image-guided radiotherapy (IGRT). Whereas only boney structures could
be visualized in the past on the treatment couch of the
linear accelerator at the time of each radiotherapy fraction, the integration of computed tomography into linear accelerator technology ("cone-beam CT”) as well as
the option to introduce radio-opaque fiducial markers
into tumors or tumor-bearing organs, such as the prostate (Figure 1), made possible the correction of the
patient position based on this information at each treatment session, thereby drastically reducing the margins
around the tumor/organ required to compensate for
motion.
Such advanced imaging on the treatment table was a
prerequisite for the clinical introduction of advanced
algorithms of dose calculation and delivery. Intensitymodulated radiotherapy (IMRT) enabled radiation physicists to create treatment plans with highly individualized
dose distributions and a sharp dose gradient at the interface of tumor volume and healthy organ, even if the latter
is virtually enclosed by the former [5]. Typical examples
include the sparing of the highly radiosensitive parotid
glands in radiotherapy of head and neck cancer and the
protection of rectal mucosa adjacent to prostate and
Page 3 of 4
seminal vesicles (Figure 2). Sophisticated target volumes
based on functional imaging data, IGRT and IMRT have
been integrated in novel radiotherapy concepts [6].
Tomotherapy, an advanced type of IMRT, integrates imaging of the patient and delivery of radiotherapy in a sectional manner [7].
Proton radiotherapy, due to advantageous physical
properties, has the potential to further improve clinical
results so far achievable with modern linear accelerator
photon radiotherapy. Like recent improvements in
photon delivery, increased (biologically effective) doses
in the tumor volume and/or reduced radiation dose in
healthy organs - as achievable with protons according to
theoretical planning studies - may further improve the
therapeutic ratio of radiotherapy. However, clinical trial
data is needed to fully assess the potential of proton
radiotherapy [8].
Individualiziation of radiotherapy concepts
In the past, based on the results of large randomized trials
and meta-analyses, specific recommendations for the
delivery of radiotherapy were made for tumor entities and
disease stages. Even today, such statements in national and
international guidelines for cancer treatment define the
standards of care. However, the assessment of tumor
Figure 2 Intensity-modulated radiotherapy (IMRT) dose distribution for prostate cancer in a sagittal CT reconstruction.
Vordermark BMC Cancer 2011, 11:503
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material in individual patients has been proposed as a predominant source of information on which to base treatment decisions. Specific combinations of biomarkers
detectable by immunohistochemistry (tissue microarrays)
and specific gene signatures detectable in gene microarray
studies have been used predominantly to predict the benefit from postoperative chemotherapy. While a focus of this
field has been to identify subgroups of breast cancer
patients benefiting from particular types of systemic therapy, response to radiotherapy has equally been addressed
by microarray studies, for example, in diseases treated
with radical radiotherapy such as cervix cancer [9].
Molecular targeting
Experimental studies of radiosensitivity of tumor cells in
in-vitro and in-vivo models have identified important
mechanisms of radioresistance. Some of these findings
could already be translated into clinically useful protocols of radiotherapy in combination with molecular targeting agents. The most prominent example is targeting
of the epithelial growth factor receptor (EGFR) in combination with radiotherapy. Initially, the association of
EGFR overexpression with prognosis was assessed in
several tumor types [10]. In a randomized trial in head
and neck cancer, EGFR targeting improved the outcome
compared to radiotherapy alone, leading to further trials
of treatment intensification with more complex drug
combinations as well as to new translational research
initiatives [11].
Low tumor oxygenation is a frequently observed cause
of poor response to radiotherapy, for example, in head and
neck or cervix cancer. Normalizing tumor oxygenation
and specifically targeting or radiosensitizing hypoxic
tumor cells have been alternative strategies to improve the
tumor control rates in hypoxic tumors. Recently, hypoxiarelated molecules have been assessed as targets in combination with radiotherapy, showing some potential for
radiosensitization of tumor cells [12].
Conclusions
Ten years of BMC Cancer have accompanied a decade of
rapid development in the field of radiation oncology and
its technical, clinical, biological and translational research
branches. While this decade has also seen dramatic
changes in the area of open-access publishing, BMC Cancer continues to be a platform for radiotherapy-related
contributions in an interdisciplinary oncology setting.
Abbreviations
CT: computed tomography; EGFR: epithelial growth factor receptor; IGRT:
image-guided radiotherapy; IMRT: Intensity-modulated radiotherapy; MRS:
magnetic resonance imaging spectroscopy; PET: positron-emission
tomography.
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Authors’ contributions
DV individually drafted and revised this manuscript.
Competing interests
The author declares that they have no competing interests.
Received: 28 April 2011 Accepted: 30 November 2011
Published: 30 November 2011
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Pre-publication history
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Cite this article as: Vordermark: Ten years of progress in radiation
oncology. BMC Cancer 2011 11:503.